Evidence map›Paper›PMID 34616046›Full record

ArticleNature biomedical engineering2021

Optimization of lipid nanoparticles for the delivery of nebulized therapeutic mRNA to the lungs.

Melissa P Lokugamage, Daryll Vanover, Jared Beyersdorf, Marine Z C Hatit, Laura Rotolo, Elisa Schrader Echeverri, Hannah E Peck, Huanzhen Ni, Jeong-Kee Yoon, YongTae Kim and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Nature biomedical engineering, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers.

0numbers the graph read from it
0cells of the map it votes in
237citing papers in PubMed
22.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

237 citing papers in PubMed, 442 citations in OpenAlex.

  1. Cas12a chRDNA-mediatedMolecular therapy. Nucleic acids · 2026
    Article
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  5. Dual pKa Lipid Nanoparticles for Lung-tropic mRNA Delivery and pH-Programmed Endosomal Escape.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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177 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Melissa P Lokugamage *Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, USA.
Daryll Vanover *Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, USA.
Jared Beyersdorf *Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, USA.
Marine Z C Hatit *Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-5713-6596
Laura RotoloWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, USA.
Elisa Schrader EcheverriWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, USA.
Hannah E PeckWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, USA.
Huanzhen NiWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, USA.
Jeong-Kee YoonGeorge W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
YongTae KimWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-8835-8247
Philip J SantangeloWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, USA. philip.santangelo@bme.gatech.edu.ORCID http://orcid.org/0000-0001-7352-0339
James E DahlmanWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, USA. james.dahlman@bme.gatech.edu.ORCID http://orcid.org/0000-0001-7580-436X
Georgia Institute of Technology · US

Funding

Highly Specific ZFN-Based HSC Gene Editing Therapies Identified By In Vivo Barcode Nanoparticle Screens And Rationally Designed MrnaUG3TR002855 · NCATS · GEORGIA INSTITUTE OF TECHNOLOGY · PI DAHLMAN, JAMES, SANTANGELO, PHILIP J · 2019 to 2021
$2.2M
Understanding the Relationship LNP Structure, Cholesterol Trafficking, and InVivo DeliveryR01GM132985 · NIGMS · GEORGIA INSTITUTE OF TECHNOLOGY · PI DAHLMAN, JAMES · 2019 to 2023
$2.0M
Highly Specific ZFN-Based HSC Gene Editing Therapies Identified By In Vivo Barcode Nanoparticle Screens And Rationally Designed MrnaUH3TR002855 · NCATS · EMORY UNIVERSITY · PI DAHLMAN, JAMES · 2022 to 2023
$1.3M
NCATS NIH HHS UG3 TR002855NCATS NIH HHS UH3 TR002855NIGMS NIH HHS R01 GM132985
6 · The paper itself

Abstract

Lipid nanoparticles (LNPs) for the efficient delivery of drugs need to be designed for the particular administration route and type of drug. Here we report the design of LNPs for the efficient delivery of therapeutic RNAs to the lung via nebulization. We optimized the composition, molar ratios and structure of LNPs made of lipids, neutral or cationic helper lipids and poly(ethylene glycol) (PEG) by evaluating the performance of LNPs belonging to six clusters occupying extremes in chemical space, and then pooling the lead clusters and expanding their diversity. We found that a low (high) molar ratio of PEG improves the performance of LNPs with neutral (cationic) helper lipids, an identified and optimal LNP for low-dose messenger RNA delivery. Nebulized delivery of an mRNA encoding a broadly neutralizing antibody targeting haemagglutinin via the optimized LNP protected mice from a lethal challenge of the H1N1 subtype of influenza A virus, and delivered mRNA more efficiently than LNPs previously optimized for systemic delivery. A cluster approach to LNP design may facilitate the optimization of LNPs for other administration routes and therapeutics.

Indexed as

Influenza A Virus, H1N1 SubtypeNanoparticlesAnimalsLiposomesLungMiceRNA, MessengerRNA, Small InterferingLipid NanoparticlesLiposomesRNA, MessengerRNA, Small Interfering

Identifiers

PMID34616046
PMCPMC10197923
OpenAlexW3204914713

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.